RGD修饰载喜树碱微粒的合成和性能研究

Synthesis and performance of RGD-modified CPT loaded microparticle

采用含二硫键的二甲基丙烯酸酯(CL)为交联剂,以呋喃保护的N-羟乙基马来酰亚胺的甲基丙烯酸酯、聚乙二醇甲基醚甲基丙烯酸酯(PEGMA)、N-乙烯基己内酰胺(VCL)、甲基丙烯酸(MAA)为共聚单体,均相聚合合成微粒。在高温条件下脱保护后,通过巯基和马来酰亚胺的加成反应制得含精氨酸-甘氨酸-天冬氨酸短肽(RGD)修饰的脱保护微粒(TMP)(RGD-TMP)。通过傅里叶红外光谱(FT-IR)、扫描电子显微镜(SEM)表征微粒结构,以喜树碱(CPT)为模型药物分析其载药能力,评价药物细胞毒性。实验结果表明:RGD-TMP粒径为100~150nm,对CPT的载药量为18.56%,在药物浓度10μg/mL的条件下,CPT的细胞存活率为91%,而RGD-TMP载CPT后的细胞存活率降至72%。在控制CPT浓度为10μg/mL情况下,RGD修饰后的载药粒子的细胞存活率由CPT的91%下降为72%,可有效提高药物的细胞毒性。

The microparticle was obtained using disulfide containing di-methacrylate（CL）as crosslinking agent,using N-hydroxcrylate maleimide protected by furan,polyethylene glycol methyl acrylate（PEGMA）,N-Vinyl-ε-caprolactam（VCL）and methacrylic acid（MAA）as monomers,vis homogeneous polymerization.After deprotection at high temperature conditions,RGD（a short peptide containing arginine glycine and asparagic acid）modified particles were obtained by addition reaction of sulfydryl and maleimide.The structure was researched by fourier infrared spectrometer（FT-IR）and scanning electron microscope（SEM）.Drug loading capacity of particles was studied using camptothecin（CPT）as the model molecules.Cytotoxicity was evaluated by the method of MTT.The results showed that the particle size was about 100-150 nm,the CPT loading efficiency was 18.56%.The cell survival rate was above90% with 250μg/mL particles.The cell survival rate of cells CPT loaded RGD-modified microparticles was 72% at the CPT concentration of 10μg/mL,while for CPT the cell survival rate was 91% at the same level.Cell study showed that RGD modification for particles could reduce the cell survival rate of CPT from 91% to 72%,at 10μg/mL CPT concentration.